Medicament dispensing device with a multimaterial diaphragm bounding a pneumatic force chamber

ABSTRACT

Provided herein is a metered dose inhaler for use with a pressurized aerosol container which is preferably breath-actuated. The metered dose inhaler contains a diaphragm which includes a central disk of a first, relatively high stiffness material and a peripheral ring, coupled by a flexure of a second, relatively low stiffness material.

CROSS-REFERENCE TO RELATED APPLICATIONS

This application is a divisional of U.S. patent application No.10/276,531, now issued as U.S. Pat. No. 7,637,260, filed Jul. 14, 2003,which is a U.S. National Phase Application of International ApplicationNo. PCT/US01/18664, filed Jun. 8, 2001, which is a Continuation ofapplication Ser. No. 09/591,321 filed Jun. 9, 2000 now U.S. Pat. No.6,553,988 issued Apr. 29, 2003, each of which are incorporated herein byreference in their entirety.

CROSS-REFERENCE TO RELATED PATENT

The subject matter in this application is related to that in U.S. Pat.No. 5,447,150. That patent is incorporated by reference.

FIELD OF THE INVENTION

This invention relates to a dispensing device, and more specifically, toa device suitable for dispensing discrete amounts of fluid. Inparticular, the invention is concerned with a dispensing device of thetype where the metered dose is administered in response to theinhalation of the patient.

BACKGROUND OF THE DISCLOSURE

Metered dose inhalers are well known in medicine for treatment, oralleviation of the effects of respiratory complaints, for exampleasthma. Breath-actuated devices are also known, and have been thesubject of many patent applications.

GB 1288971; GB 1297993; GB 1335378; GB 1383761; GB 1392193; GB 1413285;WO85/01880; GB 2204799; U.S. Pat. No. 4,803,978 and EP 0186280A describeinhalation-actuated dispensing devices for use with a pressurisedaerosol dispensing container. The device includes a dispensing containerand the container includes a valve capable of releasing a metered amountof the aerosol contents, when an internal spring operating the valve iscompressed by a sufficient amount. The dispensing device often comprisesa chamber having a mouthpiece, air inlets, actuating means for causingthe actuation of the valve in the dispensing container, a latching meansfor releasably retaining said metering valve in a charged position, andan inhalation responsive means for releasing the latch, such that ametered amount of aerosol compound is discharged into the region of themouthpiece. The overall objective is to give co-ordination of dischargeof medicament from the aerosol container with inhalation of the patient,thus allowing a maximum dose of medicament to reach the bronchialpassages of the lungs.

The latching means is often connected to a valve which moves from alatching position to a dispensing position in response to a partialvacuum developed upon inhalation.

EP-A-0045419 describes an inhalation device having biassing means whichare alone of insufficient force to depress the container but whichtogether are of sufficient force to do so.

EP-A-186280 describes a device which employs magnets to control therelease of the aerosol container.

U.S. Pat. No. 3,605,738 describes devices in which the aerosol containercommunicates with the mouthpiece via a metering chamber. A meteredquantity of the aerosol compound is discharged into the metering chamberand this is conveyed to the mouthpiece via an inhalation-actuated valve.

GB 1269554 describes a device wherein the aerosol container is moveableby a lever and cam system into a charged position held by a latch, apressure differential acting to trip the latch and move the valve of thecontainer to a discharge position.

U.S. Pat. No. 5,447,150, incorporated by reference herein, disclosed ametered dose inhaler, wherein the release of the medicament is actuatedby the inhalation of the patient. That patent disclosed aninhalation-actuated device which is more simple and compact than thethen-prior art dispensers. In one disclosed form, a closed negativepressure region is defined in part by a diaphragm molded from a singlematerial. The diaphragm includes a relatively thick central disk,surrounded by a relatively thin flexure and peripheral ring. Thatconstruction is difficult to fabricate, in part due to the differingthickness regions.

SUMMARY OF THE INVENTION

According to one aspect of the present invention there is provided animproved dispensing device for use with a drug delivery systemcomprising a means for releasing a measured dose of medicament from thesystem, the releasing means comprising a means for applying a preloadcapable of actuating the delivery means in the system, a means forapplying a resisting pneumatic force capable of preventing actuation ofthe delivery means and a release device capable of freeing the resistingpneumatic force to allow the preload to actuate the delivery means anddispense the medicament. The means for applying a resisting pneumaticforce of the present invention is similar to that in U.S. Pat. No.5,447,550 but includes a structure that is distinct from, and providessubstantial improvement over, the corresponding structure in U.S. Pat.No. 5,447,150.

The pneumatic resisting means of the present invention is provided byair which is held at a negative pressure below atmospheric prior torelease. That negative pressure provides a pneumatic resisting forcewhich opposes the preload force. The release device acts to return thepressure to atmospheric or prior equilibrium, thus allowing the fullforce of the preload to act. The pneumatic resisting force isestablished by a negative pressure region defined in part by adiaphragm. The diaphragm includes a central disk of a first, relativelyhigh stiffness material and a peripheral ring, coupled by a flexure of asecond, relatively low stiffness material. In, various forms, theperipheral ring may be of the same material as the flexure, or may be ofa different material.

The device is particularly suited for use with pressurized inhalationaerosols having valves as the delivery means.

Although this device has been described in particular relation to asystem using air, it will be realized that in a closed system anysuitable gas could be used.

In a preferred arrangement, there is provided a breath actuateddispensing device for use with an aerosol medicament container fordispensing a medicament in a metered dose. The container is cylindricaland extends along a container axis between a first end and a second end.The container has a spring based aerosol valve at the first end, whichis responsive to an axial force above a predetermined threshold torelease the metered dose. The device includes a housing disposed about acentral axis and having a first end and a second end, where the secondend includes a shoulder and an expulsion nozzle extending therethrough.A support sleeve is disposed within the housing. The sleeve is adaptedfor axial motion along the central axis. The sleeve is further adaptedto support the second end of the container, whereby the container axisis substantially coaxial with the central axis and the aerosol valve ispositioned adjacent the shoulder and in communication with the expulsionnozzle.

The device further includes a diaphragm assembly having a relativelyrigid central disk, a peripheral attachment ring disposed about aperipheral portion of the disk, and an annular flexure extending betweenthe peripheral portion of the disk and the attachment ring. The centraldisk is affixed to the first end of the housing and the peripheral ringis affixed to the sleeve, thereby defining a closed region between thediaphragm and the sleeve. A breath actuated valve assembly is providedto selectively establish in a first state an air flow path between theclosed region and regions exterior thereto, and interrupting in a secondstate the air flow path. A spring force bias element is adapted to biasthe sleeve toward the second'end of the housing. When the breathactuated valve element is in the second state, pneumatic pressure in theclosed region establishes a force on the sleeve equal opposite the biasand of a magnitude less than or equal to the bias. In that circumstance,the axial force on the aerosol valve is below the predeterminedthreshold, and whereby when the breath actuated valve element is in thefirst state, pneumatic pressure in the closed region establishes asubstantially zero force on the sleeve and the bias is sufficient todrive the sleeve and the container toward the shoulder and establish anaxial force on the aerosol valve above the predetermined threshold.

Preferably, the central disk is made of a first material characterizedby a relatively high stiffness, and the annular flexure is made of asecond material characterized by a relatively low stiffness. The annularflexure is bonded to the disk, whereby the disk, the annular flexure andthe peripheral ring form a contiguous assembly. In an alternative form,the ring and flexure may be different material as well.

Preferably, the multimaterial diaphragm is made using a multishotmolding process wherein a first portion (such as the disk) is molded ina first step, and a second portion (such as the flexure and ring) aremolded in a second step, and at the same time bonded to the firstportion.

It is also preferred that the release device is breath-actuated in orderto co-ordinate the release of the medicament with the intake of breath.The favored breath-actuating means comprises a moveable vane mechanism.This vane mechanism may be housed in the upper part of the chamber. Avalve seal is preferably attached to said vane, such that on inhalationthe vane moves from its rest position to its actuating position, thusmoving the valve seal out of contact with the valve port, causing theopening of the valve. The vane mechanism is preferably dynamicallybalanced, and may be biased towards its closed position, e.g. by aspring. When the valve opens, an air flow path is established betweenthe negative pressure region and regions exterior thereto.

The outer chamber may include air inlets allowing passage of air to themouthpiece of the device. The inlets may take the form of slots or of anair porous membrane. The latter is particularly suitable to help filterdust.

The medicament may be a drug per se or on any form of carrier, e.g.including a powder or a gaseous carrier.

BRIEF DESCRIPTION OF THE DRAWINGS

For a fuller understanding of the nature and the objects of theinvention, reference should be made to the following detaileddescription and the accompanying drawings in which like referencenumerals refer to like elements and in which:

FIG. 1 is a section view of an inhaler according to an embodiment of theinvention;

FIG. 2 shows an enlarged view of a diaphragm for use with the embodimentshown in FIG. 1;

FIG. 3 shows an enlarged section view of the diaphragm in position inpre-actuated and actuated state;

FIG. 4 shows a top plan view of another diaphragm for use with aninhaler according to an embodiment of the invention;

FIG. 5 shows a top perspective view of the diaphragm of FIG. 4;

FIG. 6 shows a sectional view of the diaphragm taken along line 6-6 ofFIG. 4;

FIG. 7 shows a sectional view of the diaphragm taken along line 7-7 ofFIG. 4; and

FIG. 8 shows an enlarged section view of the diaphragm of FIG. 4 inposition in a pre-actuated state within an actuator assembly of aninhaler according to an embodiment of the invention.

DESCRIPTION OF THE PREFERRED EMBODIMENTS

In an arrangement as shown in FIG. 1, an inhalation device consists of amain body 400, which is generally cylindrical in cross section, with amouthpiece section 405 at one end and an end cap 407 housing air inlets420 at the other end. A known type of aerosol dispensing container 25 ofgenerally cylindrical shape is housed within the main body of thedevice. The aerosol dispensing container has a stem 40 which contains anaerosol dispensing valve (not shown). The bore 15 is such that it formsan air tight seal on the stem 40 of the aerosol dispensing container 25.A shoulder 45 limits and locates the position of the stem 40, which inturn locates the aerosol dispensing container 25 in position in the mainbody 400. A passage 50 extends from the bore 15, continuing from theshoulder 45 to interconnect with a dispensing nozzle 55.

The opposite end of the dispensing container is contained within asleeve 421 of similar cross section to the main body 400. Thelongitudinal axis of both the sleeve 421 and main body 400 is generallycoaxial. The sleeve is in loose sliding contact with the inner wall ofthe main body and may include several rebated grooves 430 in its wallsto allow free passage of air in the main body past the sleeve. Thesleeve 421 may be held in place by connection with a diaphragm 440 heldin connection with the top of the main body 400, as will now bedescribed. Thus, the sleeve 421 effectively hangs from the top of themain body.

One end of an e.g., molded flexible diaphragm 440 (as shown alone inFIG. 2) comprising a rigid disc-like section 441, a flexible generallycylindrical wall section 445 and a diaphragm connection section 447, isfitted around a inner sleeve groove 450 in the sleeve, e.g. bysnap-fitting. A further molded lip 470 on the diaphragm 440 provides asnug fit for one end of a compression spring 460. The compression springis thus located and free to act on the sleeve. The other end of thecompression spring is located by an annular shoulder 481 in apredominantly cylindrical flanged insert 480 housed in the top sectionof the main body 400. This insert includes a groove 490 into which thedisc-Like section 441 of the flexible diaphragm 440 is snap-fitted.Preferably, the multimaterial diaphragm is made using a multishotmolding process wherein a first portion (such as the disk) is molded ina first step, and a second portion (such as the flexure and ring) ismolded in a second step, and at the same time bonded to the firstportion.

With the improved diaphragm configuration of the invention, shown inFIG. 2, the relatively thick disk-portion “A” is molded from a rigidmaterial (relatively high stiffness), which is particularly resistant toflexural deformation when the closed region 600 is at negative pressure,while the relatively thin flexure portion “B” is molded from anoptimally flexible (relatively low stiffness) material, minimising theforce required to move the inner sleeve and hence the forces required tobe stored and released by the mechanism. The relatively thin flexureportion “B” is bonded to the disk-portion “A” along a continuous surfacesubstantially parallel to the central axis of the diaphragm.

The joint between the diaphragm connector section 447 and inner sleevegroove 450 is arranged to be air tight and the shape of the top surfaceof.the sleeve 422 to conform to the internal shape of the diaphragm suchthat in the rest position of the inhaler the two surfaces are in closeproximity, and the enclosed space between them very small.

The cylindrical flanged insert 480 is retained in place by the end cap407 fitted into the main body of the device. This forms a chamber 590between the air inlet slots 420 and the rigid part 441 of the diaphragm.The chamber is provided with one or more air pathways 580 such that airmay pass from the air, inlet slots 420 to the mouthpiece 405. The rigiddisc-like section 441 of the diaphragm also includes a small valve port495 which is normally covered by a valve seal (flap) 540 housed in avane 550 pivotally connected to the cylindrical flanged insert 480.

The vane 550 in its rest position divides the chamber 590 between theair inlets 420 and the air pathways 580 that link to the mouthpiece suchthat it may move from its rest position by means of a pressure dropbetween the air inlets and the mouthpiece. On movement of the vane tothe actuated position the valve seal (flap) 540 is sufficiently moved toopen the valve port 495. (The vane 550 may be biased closed by a lightspring flexure, a weight or a magnet not shown.)

As shown in FIG. 1, the end of the main body having a pivot 500 has arecess adapted to receive a cam 520 integral with a dust cap 510operating on the pivot. The recess further includes a passagecommunicating with a similar passage molded into the internal wall ofthe main body 400. A camfollower 530 extending from the lower edge ofthe inner sleeve 421 acts on the cam such that when the dust cap is inthe closed position the inner sleeve is forced by the camfollower to itsuppermost position.

When the dust cap is rotated to its open position the cam profile issuch that the camfollower is free to move downwards by an amountsufficient to allow actuation of the device.

In its rest position the dust cap 510 is closed, the camfollower 530restrains the inner sleeve 421 in its uppermost position such that theenclosed space trapped between the diaphragm 440 and the top surface 422of the inner sleeve is at a minimum and the spring 460 is compressed.The valve port 495 is closed by the valve seal (flap) 540 and the sleeve421 is clear of the top of the aerosol can 25 which is thus unloaded.

The dust cap is opened rotating the integral cam 520 allowing thecamfollower 530 to drop by amount AA. The inner sleeve is forceddownwards under the action of the spring 460. As the inner sleeve movesdownwards the enclosed volume between the diaphragm 440 and inner sleeveis increased by a linear equivalent amount A′A′, less than or equal toAA. Since the valve port 495 is closed this creates a low pressurevolume or near vacuum in the closed region 600 [FIG. 3]. The effect ofthe pressure differential between the closed region 600 and atmosphericpressure is such that the inner sleeve tends to resist the action of thespring. As the inner sleeve moves downwards it contacts the aerosol can25 and begins compression of the aerosol valve (not shown).

Downward movement of the inner sleeve will continue until there is abalance of forces between the compressive force in the spring 460 andresisting forces created by the pressure differential and compression ofthe aerosol valve. The geometry of the device is arranged such that thisbalance occurs before the aerosol valve has been sufficiently compressedto actuate it.

A typical Chlorofluorocarbon (CFC) aerosol medicament container requiresabout 20N force to actuate, while a typical hydrofluoroalkane (HFA)aerosol medicament container requires about 40N force to actuate. Thus,depending upon the application, the spring 460 should provide a force10% to 50% greater than the required actuation force of the medicamentcontainer. As is known, CFC containing propellants have been shown toliberate chlorine in the stratosphere and cause ozone depletion. Becauseof this danger, the Montreal Protocol was signed that bans the use ofCFCs. Metered-dose inhalers (MDIs) for treating asthma and otherrespiratory diseases were exempted from this general ban, although thisexemption is temporary and will be lifted as substitute products becomeavailable. The first such substitute, HFA propellant, has been on themarket for about a year.

It may also be possible to arrange for the balance of forces to takeplace before the inner sleeve has contacted the aerosol can, such thatthe spring force is balanced by the resisting force produced on theinner sleeve by virtue of the pressure differential.

On inhalation by the patient through the mouthpiece 405, a smallpressure differential is created across the vane 550 which is pivotedtowards one end. The pressure differential causes the vane to move fromthe rest position to the actuated position. The vane 550 and design ofthe air passageway 580 in the chamber 590 are such that in the actuatedposition air can flow freely from the air inlets 420 to the patient.

The movement of the vane 550 causes the valve seal (flap) 540 to bemoved out of a sealing position with the valve port 495. Opening thevalve port allows air into the closed region 600 between the diaphragmand inner sleeve such that the enclosed space reaches atmosphericpressure. This causes an imbalance of forces acting on the sleeve 421and container 25. The sleeve and container are thus forced downwards bythe spring 460 resulting in the release of a measured dose of medicamentthrough the dispensing nozzle 55 and into the mouthpiece at the sametime as the patient breathes in. Thus, the patient inhales air with ametered dose of medicament.

After the inhalation of the dose by the patient, the dust cap 510 isreturned to its closed position. This rotates the cam 520 and causes thecamfollower 530 to be forced upwards. This in turn acts on the innersleeve 421 moving it upwards to compress the spring 460 and close theclosed region 600 between the diaphragm and inner sleeve top surface422. This forces air out of the closed region 600 which escapes throughthe valve port 495 lifting the valve seal (flap) 540. Since the valveseal (flap) is only lightly biased to its closed position it presentslittle resistance to air flow out of the enclosed space. The aerosol canis free to return to the rest position under the action of its ownaerosol valve spring.

In use the patient loads the aerosol dispensing container into the mainbody. The aerosol container may be loaded by providing a coarse threadedscrew in the main body 400, for example about the line I-I. When part ofthe main body 400 has been unscrewed, the aerosol can be inserted. Themain body 400 can then be replaced locating the inner sleeve over thetop end of the can, and the device is ready for use. As describedpreviously, the device could be manufactured as a sealed unit.

The device may be provided with means to provide a regulated air flow tothe user or inhaler. Thus a sonic device, e.g., a reed, may be providedwhich sounds when the inspired air flow is greater than a pre-set level,e.g., above 30 to 50 litres per minute. The sonic device may be locatedin the mouthpiece 95 or below the air inlet 421. The sound producedwarns the patient to breathe at a lower rate.

The device may be provided with means to provide a regulated air flow tothe user or inhaler. Thus a sonic device, e.g., a reed, may be providedwhich sounds when the inspired air flow is greater than a pre-set level,e.g., above 30 to 50 litres per minute. The sonic device may be locatedin the mouthpiece 405 or below the air inlet 420. The sound producedwarns the patient to breathe at a lower rate.

The main body of a dispensing device, as described in the aboveembodiment of this invention is preferably manufactured from a plasticsuch as polypropylene, acetal or moulded polystyrene. It may however bemanufactured from metal or another suitable material.

Referring to FIGS. 4-8 another diaphragm assembly 640 and actuatorassembly according to the present invention for use with the medicamentdispenser of FIG. 1 are shown. The diaphragm assembly 640 and theactuator assembly of FIGS. 4-8 are similar to the diaphragm assembly 440and the actuator assembly of FIGS. 2 and 3, such that similar elementsare provided with the same reference numerals.

The molded flexible diaphragm 640 includes a rigid disc-like section641, a flexible generally cylindrical wall section, or annular flexure645, and a thicker connector section, or peripheral attachment ring 647.A central portion 700 is unitarily formed with and extends radiallyinwardly from the annular flexure 645. The central portion preferably isprovided in the form of a central portion 700 bonded along a top surfaceto a bottom surface of the rigid disc-like section 641, i.e., surfacessubstantially traverse to the central axis of the diaphragm 640.

Referring to FIGS. 6 and 7, the relatively thick disk-portion “A” whichincludes the disc-like section 641 of the diaphragm 640, is molded froma rigid material (relatively high stiffness) such as AcrylonitrileButadiene Styrene (ABS), which is particularly resistant to flexuraldeformation when the closed region 600 is at negative pressure. Therelatively thin flexure portion “B” which includes the central portion700, the annular flexure 645 and the peripheral attachment ring 647, ismolded from an optimally flexible material (relatively low stiffness)such as a thermoplastic elastomer (TPE), permitting high performance.Preferably, the multimaterial diaphragm 640 is made using a multishotmolding process wherein the first portion “A” is molded in a first step,and the second portion “B” is molded in a second step, and at the sametime bonded to the first portion.

As shown in FIGS. 4 through 7, the central portion 700 and the rigiddisc-like section 641 both define a central upwardly extending boss 702for additional strength. In addition, the rigid disc-like section 641includes an outer axial wall 704 which provides further strength to thediaphragm 640. The central portion 700 includes axial walls 706 whichare received within and bonded to axial grooves 708 of the rigiddisc-like section 641, thereby providing bonding surfaces substantiallyparallel with the central axis of the diaphragm 640 and increasing thetotal bonding surface area between the central portion 700 and the rigiddisc-like section 641.

Referring also to FIG. 8, the peripheral attachment ring 647 of thediaphragm 640 is fitted around an annular wall 451 of the sleeve 421 andis secured in an air-tight manner thereon with a retainer ring 800,which is secured to the sleeve 421, e.g., by snap-fitting into anannular groove 452 of the sleeve. The retainer ring 800 also provides asnug fit for one end of the compression spring 460, such that thecompression spring is thus located and free to act on the sleeve 421.The cylindrical flanged insert 480 housed in the top section of the mainbody 400 of the inhaler includes a protrusion 491 which is snap fit intoa radially outwardly facing circumferential groove 710 of the relativelyrigid disc-like section 641 of the flexible diaphragm 640.

The valve port 690 of the diaphragm 640 passes through the rigiddisc-like section 641 and the central portion 700 of the diaphragm. Thevalve port 690 is closed by the valve seal (flap) 540, which is biasedclosed by a fiat spring 802, as shown in FIG. 8. The rigid disc-likesection 641 of the diaphragm includes protrusions 712 extending upwardlytherefrom that receive and correctly position the flat spring 802. Therigid disc-like section 641 of the diaphragm 640 also includes a baffle714 on a top surface thereof for substantially preventing air flowbetween the valve seal (flap) 540 and the diaphragm. The baffle 714closely follows the profile of the underside of the flap 540, yetprovides sufficient clearance for the flap to open uponbreath-actuation. The rigid disc-like section 641 of the diaphragm 640additionally includes an assembly location key 716 for use in correctlyassembling the diaphragm 640 within the actuator assembly of FIG. 8.

The invention may be embodied in other specific forms without departingfrom the spirit or essential characteristics thereof. The presentembodiments are therefore to be considered in all respects illustrativeand not restrictive, the scope of the invention being indicated by theappended claims rather than by the foregoing description, and allchanges which come within the meaning and range of equivalency of theclaims are therefore intended to be embraced therein.

Although the invention herein has been described with reference toparticular embodiments, it is to be understood that these embodimentsare merely illustrative of the principles and applications of thepresent invention. It is therefore to be understood that numerousmodifications may be made to the illustrative embodiments and that otherarrangements may be devised without departing from the spirit and scopeof the present invention as defined by the appended claims.

1. A diaphragm for defining a closed region within a medicamentdispensing device including a main body, a sleeve movably positionedwithin said main body, and a spring operatively positioned in said mainbody to apply a preload force to said sleeve, said diaphragm comprising:a relatively rigid central disk made of a first material having arelatively high stiffness, and adapted to be affixed to an inner end ofsaid main body of said medicament dispensing device; a peripheralattachment ring disposed about a peripheral portion of said disk andadapted to be attached to a closed end of said sleeve of said medicamentdispensing device; and an annular flexure made of a second materialhaving a relatively low stiffness, and extending between said peripheralportion of said disk and said attachment ring to thereby define a closedregion between said diaphragm and said closed end of said sleeve; andwherein said annular flexure is bonded to said disk, and wherein saiddisk, said annular flexure and said peripheral ring form a contiguousassembly.
 2. A diaphragm according to claim 1, wherein the diaphragmdefines a valve port for providing fluid communication between saidinner end of said main body and said closed region.
 3. A diaphragmaccording to claim 1, wherein said peripheral ring is made of saidsecond material and unitarily formed with said annular flexure.
 4. Adiaphragm according to claim 1, wherein said annular flexure is bondedto said disk along at least one bonding surface substantially parallelto a central axis of said diaphragm.
 5. A diaphragm according to claim4, wherein said at least one bonding surface comprises a continuoussurface axially arranged with respect to said central axis.
 6. Adiaphragm according to claim 1, wherein said annular flexure is bondedto said disk along at least one bonding surface substantially traverseto a central axis of said diaphragm.
 7. A diaphragm for defining aclosed region within a medicament dispensing device including a mainbody, a sleeve movably positioned within said main body, and a springoperatively positioned in said main body to apply a preload force tosaid sleeve, said diaphragm comprising: a relatively rigid central diskmade of a first material having a relatively high stiffness, and adaptedto be affixed to an inner end of said main body of said medicamentdispensing device:, a peripheral attachment ring disposed about aperipheral portion of said disk and adapted to be attached to a closedend of said sleeve of said medicament dispensing device; and an annularflexure made of a second material having a relatively low stiffness, andextending between said peripheral portion of said disk and saidattachment ring to thereby define a closed region between said diaphragmand said closed end of said sleeve; said diaphragm further comprising acentral portion that is made of said second material and unitarilyformed with and extending radially inwardly from said annular flexure,said central portion bonded to said disk along at least one bondingsurface substantially traverse to a central axis of said diaphragm; andwherein said disk, said annular flexure and said peripheral ring form acontiguous assembly.
 8. A diaphragm according to claim 7, wherein saidcentral portion is in the form of a disk.
 9. A diaphragm according toclaim 7, wherein said central portion is also bonded to said disk alongat least one surface substantially parallel to said central axis.
 10. Adiaphragm according to claim 9, wherein said central portion includes atleast one annular wall coaxially arranged with respect to said centralaxis and received within an annular groove of said disk, said annularwall bonded to said disk along the at least one surface substantiallyparallel to said central axis.
 11. A diaphragm according to claim 7,wherein the diaphragm defines a valve port for providing fluidcommunication between said inner end of said main body and said closedregion, and wherein said valve port passes through said central portionand said disk.
 12. A method of forming and assembling a diaphragm of amedicament dispensing device comprising the steps of: forming arelatively rigid central disk from a first material having a relativelyhigh stiffness; forming a diaphragm component from a second materialhaving a relatively low stiffness, the diaphragm component including acentral segment, an annular flexure segment extending circumferentiallyabout a peripheral portion of the central segment, and a peripheral ringsegment extending circumferentially about a peripheral portion of theannular flexure segment, wherein the peripheral ring segment is disposedabout the annular flexure segment to form a substantially cylindricaland contiguous component; bonding the central disk to a mounting surfaceof the central portion of the diaphragm component to form the diaphragm;and positioning the diaphragm in a medicament dispensing device.
 13. Themethod of claim 12, wherein the bonding step includes bonding thecentral disk to the mounting surface of the diaphragm component along atleast one surface of the mounting surface that is substantially parallelto a central axis of the diaphragm.
 14. The method of claim 12, whereinthe bonding step includes bonding the central disk to the mountingsurface of the diaphragm component along at least one surface of themounting surface that is substantially traverse to a central axis of thediaphragm.
 15. The method of claim 12, wherein the bonding step includesbonding an annular wall formed on the mounting surface to acorresponding annular groove formed on the central disk.